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(Circulation. 2000;101:e120.)
© 2000 American Heart Association, Inc.

Circulation Electronic Pages

Is Acquired Activated Protein C Resistance a Cardiovascular Risk?

Kazuomi Kario, MD, PhD

Hypertension Center Department of Internal Medicine, Cornell University Medical College/The New York Presbyterian Hospital, New York, NY

Toshiyuki Sakata, PhD

Laboratory of Clinical Chemistry National Cardiovascular Center, Osaka, Japan

Toshiyuki Miyata, PhD

Research Institute National Cardiovascular Center, Osaka, Japan

	Introduction

 
To the Editor:

We have read the article by Kiechl et al¹ demonstrating that acquired activated protein C resistance (APC) may be a risk factor for atherosclerosis and arterial thrombosis in whites. We² previously demonstrated that acquired APC resistance is associated not only with venous thrombosis (deep vein thrombosis and pulmonary thromboembolism) but also with arterial thrombotic disease (cerebral infarction and coronary artery disease) in the Japanese population. It is well known that no Japanese has factor V Leiden mutation because of the founder effect of this mutation.³ Thus, it is likely that in Japanese, some environmental factors might contribute to APC resistance. In addition, we demonstrated a positive association of APC sensitivity ratio with plasma levels of the activated form of factor VII (FVIIa, an activation marker of the early phase of the tissue factor pathway of coagulation⁴ in healthy subjects; correlation coefficient -0.38, P<0.05, n=33).² This association was also found in subjects with a predisposing condition of thrombosis, namely, protein C deficiency (correlation coefficient -0.40, P<0.005, n=53). More recently, pregnancy-related APC resistance has also been reported⁵ to be associated with thrombin-antithrombin complex (an indicator of in vivo thrombin generation) (correlation coefficient with APC sensitivity ratio -0.274, P=0.01, n=128). Thus, the APC resistance may reflect the global insensitivity of APC and may provide a good method to assess the hypercoagulable state in vivo. The hypercoagulable state induced by acquired APC resistance should be given greater emphasis in clinical practice in the future.

	References

 
1. Kiechl S, Muigg A, Santer P, Mitterer M, Egger G, Oberhollenzer M, Oberhollenzer F, Mayr A, Gasperi A, Poewe W, Willeit J. Poor response to activated protein C as a prominent risk predictor of advanced atherosclerosis and arterial disease. Circulation. 1999;99:614–619.[Abstract/Free Full Text]

2. Sakata T, Kario K, Katayama Y, Matsuyama T, Kato H, Miyata T. Clinical significance of activated protein C resistance as a potential marker for hypercoagulable state. Thromb Res. 1996;82:235–244.[Medline] [Order article via Infotrieve]

3. Fujimura H, Kambayashi J, Monden M, Kato H, Miyata T. Coagulation factor V Leiden mutation may have a racial background. Thromb Haemost. 1995;74:1381–1382.[Medline] [Order article via Infotrieve]

4. Kario K, Sakata T, Matsuo T, Miyata T. Factor VII in non-insulin-dependent diabetic patients with microalbuminuria. Lancet. 1993;342:1552. Letter.[Medline] [Order article via Infotrieve]

5. Clark P, Walker ID, Greer I. Acquired activated protein-C resistance in pregnancy and association with increased thrombin generation and fetal weight. Lancet. 1999;353:292–293.

Response

Stefan Kiechl, MD; Johann Willeit, MD

Department of Neurology, University Clinic Innsbruck, Innsbruck, Austria

	Introduction

 
Kario et al emphasized . . . [Full Text of this Article]